Growth differentiation factor 9 (GDF-9) is a recently-identified member of the TGFβ superfamily, which encompasses a large group of growth and differentiation factors that play important roles in regulating embryonic development and in maintaining tissue homeostasis in adult mammals. These factors are synthesized as pre-propeptides, forming dimers in the mature, secreted form. In this dimeric state, GDF proteins are able to interact with various cell surface receptors, thereby modulating a variety of cellular processes. Several TGFβ family members have been found to have tissue-specific expression related to the function of the factor. For example, GDF-8, a negative regulator of skeletal muscle growth, is specifically expressed in cells from skeletal tissue (McPherron, A. C., et al., Nature 387: 83–90, 1997).
The precise function of GDF-9 remains unclear, but the distribution of its gene product is known to be restricted to only a few tissues, particularly the ovary (and in the testes and the hypothalamus at very low levels). In humans, expression is also observed in the pituitary and placenta (Fitzpatrick et al., Endocrinology 139: 2571–2578, 1998). Studies in transgenic mice have found that disruption of the GDF-9 gene results in the prevention of normal follicular development beyond an early stage, resulting in infertility in females (Dong et al., Nature 383: 531–535, 1996; Carabatsos et al., Developmental Biology 204: 373–384, 1998). No data is currently available about the role of GDF-9 in the testes, but male GDF-9-deficient mice exhibit normal fertility.